Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8ZPCNS)

DOT Name Serine/threonine-protein kinase Chk2 (CHEK2)
Synonyms EC 2.7.11.1; CHK2 checkpoint homolog; Cds1 homolog; Hucds1; hCds1; Checkpoint kinase 2
Gene Name CHEK2
Related Disease
Hereditary breast carcinoma ( )
Li-Fraumeni syndrome ( )
Obsolete Li-Fraumeni syndrome 2 ( )
Acute myelogenous leukaemia ( )
Colorectal cancer ( )
Familial ovarian cancer ( )
Hereditary nonpolyposis colon cancer ( )
UniProt ID
CHK2_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
1GXC ; 2CN5 ; 2CN8 ; 2W0J ; 2W7X ; 2WTC ; 2WTD ; 2WTI ; 2WTJ ; 2XBJ ; 2XK9 ; 2XM8 ; 2XM9 ; 2YCF ; 2YCQ ; 2YCR ; 2YCS ; 2YIQ ; 2YIR ; 2YIT ; 3I6U ; 3I6W ; 3VA4 ; 4A9R ; 4A9S ; 4A9T ; 4A9U ; 4BDA ; 4BDB ; 4BDC ; 4BDD ; 4BDE ; 4BDF ; 4BDG ; 4BDH ; 4BDI ; 4BDJ ; 4BDK
EC Number
2.7.11.1
Pfam ID
PF00498 ; PF00069
Sequence
MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTL
SSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKS
CEYCFDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYIEDHSGNGTFVNTELVGKGKR
RPLNNNSEIALSLSRNKVFVFFDLTVDDQSVYPKALRDEYIMSKTLGSGACGEVKLAFER
KTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIV
LELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKPENVLLSSQEE
DCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDCWSLGVILFIC
LSGYPPFSEHRTQVSLKDQITSGKYNFIPEVWAEVSEKALDLVKKLLVVDPKARFTTEEA
LRHPWLQDEDMKRKFQDLLSEENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCA
AVL
Function
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition ; (Microbial infection) Phosphorylates herpes simplex virus 1/HHV-1 protein ICP0 and thus activates its SUMO-targeted ubiquitin ligase activity.
Tissue Specificity High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.
KEGG Pathway
Cell cycle (hsa04110 )
p53 sig.ling pathway (hsa04115 )
Cellular senescence (hsa04218 )
Human T-cell leukemia virus 1 infection (hsa05166 )
Reactome Pathway
Regulation of TP53 Activity through Phosphorylation (R-HSA-6804756 )
Regulation of TP53 Degradation (R-HSA-6804757 )
Regulation of TP53 Activity through Methylation (R-HSA-6804760 )
G2/M DNA damage checkpoint (R-HSA-69473 )
Stabilization of p53 (R-HSA-69541 )
Ubiquitin Mediated Degradation of Phosphorylated Cdc25A (R-HSA-69601 )
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B (R-HSA-75035 )
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks (R-HSA-5693565 )

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Hereditary breast carcinoma DISAEZT5 Definitive Autosomal dominant [1]
Li-Fraumeni syndrome DISR64XA Definitive Autosomal dominant [2]
Obsolete Li-Fraumeni syndrome 2 DISOFNTT Definitive Autosomal recessive [3]
Acute myelogenous leukaemia DISCSPTN Moderate Autosomal dominant [4]
Colorectal cancer DISNH7P9 Moderate Autosomal dominant [3]
Familial ovarian cancer DISGLR2C Disputed Autosomal dominant [1]
Hereditary nonpolyposis colon cancer DISPA49R Limited Autosomal dominant [1]
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⏷ Show the Full List of 7 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
26 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the methylation of Serine/threonine-protein kinase Chk2 (CHEK2). [5]
Temozolomide DMKECZD Approved Temozolomide increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [11]
Hydrogen peroxide DM1NG5W Approved Hydrogen peroxide increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [13]
Etoposide DMNH3PG Approved Etoposide increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [17]
Irinotecan DMP6SC2 Approved Irinotecan increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [18]
Mitomycin DMH0ZJE Approved Mitomycin increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [19]
Melphalan DMOLNHF Approved Melphalan increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [19]
Hydroxyurea DMOQVU9 Approved Hydroxyurea increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [22]
Artesunate DMR27C8 Approved Artesunate increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [24]
Bleomycin DMNER5S Approved Bleomycin increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [13]
Silymarin DMXBYQR Phase 4 Silymarin increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [30]
Resveratrol DM3RWXL Phase 3 Resveratrol increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [31]
Curcumin DMQPH29 Phase 3 Curcumin increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [32]
Rigosertib DMOSTXF Phase 3 Rigosertib increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [34]
VAL-083 DM9J5Q4 Phase 3 VAL-083 increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [35]
Genistein DM0JETC Phase 2/3 Genistein increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [36]
Mivebresib DMCPF90 Phase 1 Mivebresib increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [39]
TAK-114 DMTXE19 Phase 1 TAK-114 increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [40]
Wortmannin DM8EVK5 Terminated Wortmannin decreases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [44]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the methylation of Serine/threonine-protein kinase Chk2 (CHEK2). [45]
[3H]methyltrienolone DMTSGOW Investigative [3H]methyltrienolone increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [48]
2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE DMNQL17 Investigative 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [22]
N-nonylphenol DMH3OUX Investigative N-nonylphenol increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [22]
Dorsomorphin DMKYXJW Investigative Dorsomorphin increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [52]
Tetramethylbutylphenol DMW9CH2 Investigative Tetramethylbutylphenol increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [22]
NORCANTHARIDIN DM9B6Y1 Investigative NORCANTHARIDIN increases the phosphorylation of Serine/threonine-protein kinase Chk2 (CHEK2). [54]
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⏷ Show the Full List of 26 Drug(s)
33 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Acetaminophen DMUIE76 Approved Acetaminophen increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [6]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [7]
Cupric Sulfate DMP0NFQ Approved Cupric Sulfate decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [8]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [9]
Estradiol DMUNTE3 Approved Estradiol decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [10]
Arsenic trioxide DM61TA4 Approved Arsenic trioxide increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [12]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [14]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [14]
Cannabidiol DM0659E Approved Cannabidiol decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [15]
Aspirin DM672AH Approved Aspirin increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [16]
Zidovudine DM4KI7O Approved Zidovudine decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [20]
Capsaicin DMGMF6V Approved Capsaicin increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [21]
Testosterone Undecanoate DMZO10Y Approved Testosterone Undecanoate decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [23]
Dihydroxyacetone DMM1LG2 Approved Dihydroxyacetone decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [25]
Digitoxin DMWVIGP Approved Digitoxin decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [26]
Floxuridine DM04LR2 Approved Floxuridine increases the activity of Serine/threonine-protein kinase Chk2 (CHEK2). [27]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [28]
Berberine DMC5Q8X Phase 4 Berberine increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [29]
Camptothecin DM6CHNJ Phase 3 Camptothecin increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [33]
UCN-01 DMUNJZB Phase 2 UCN-01 decreases the activity of Serine/threonine-protein kinase Chk2 (CHEK2). [37]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [38]
LMP400 DM4FW2E Phase 1 LMP400 increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [33]
AZD7762 DM1FW0C Phase 1 AZD7762 decreases the activity of Serine/threonine-protein kinase Chk2 (CHEK2). [37]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [41]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the activity of Serine/threonine-protein kinase Chk2 (CHEK2). [42]
Dioscin DM5H2W9 Preclinical Dioscin decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [43]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [46]
Formaldehyde DM7Q6M0 Investigative Formaldehyde decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [47]
acrolein DMAMCSR Investigative acrolein increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [49]
3,7,3',4'-TETRAHYDROXYFLAVONE DMES906 Investigative 3,7,3',4'-TETRAHYDROXYFLAVONE increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [50]
Morin DM2OGZ5 Investigative Morin decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [51]
USNIC ACID DMGOURX Investigative USNIC ACID increases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [53]
KU-55933 DMDT42X Investigative KU-55933 decreases the expression of Serine/threonine-protein kinase Chk2 (CHEK2). [55]
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⏷ Show the Full List of 33 Drug(s)

References

1 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
2 Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome. Cancer Res. 2001 Nov 15;61(22):8062-7.
3 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
4 The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
5 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
6 Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
7 Exploring pradimicin-IRD antineoplastic mechanisms and related DNA repair pathways. Chem Biol Interact. 2023 Feb 1;371:110342. doi: 10.1016/j.cbi.2023.110342. Epub 2023 Jan 10.
8 Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
9 Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):117-27.
10 Molecular mechanism of action of bisphenol and bisphenol A mediated by oestrogen receptor alpha in growth and apoptosis of breast cancer cells. Br J Pharmacol. 2013 May;169(1):167-78.
11 Akt activation suppresses Chk2-mediated, methylating agent-induced G2 arrest and protects from temozolomide-induced mitotic catastrophe and cellular senescence. Cancer Res. 2005 Jun 1;65(11):4861-9. doi: 10.1158/0008-5472.CAN-04-2633.
12 Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells. Toxicol Appl Pharmacol. 2012 Jun 1;261(2):204-16.
13 Direct activation of ATM by resveratrol under oxidizing conditions. PLoS One. 2014 Jun 16;9(6):e97969. doi: 10.1371/journal.pone.0097969. eCollection 2014.
14 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
15 Cannabidiol-induced transcriptomic changes and cellular senescence in human Sertoli cells. Toxicol Sci. 2023 Feb 17;191(2):227-238. doi: 10.1093/toxsci/kfac131.
16 Lunasin, a novel seed peptide, sensitizes human breast cancer MDA-MB-231 cells to aspirin-arrested cell cycle and induced apoptosis. Chem Biol Interact. 2010 Jul 30;186(2):127-34. doi: 10.1016/j.cbi.2010.04.027. Epub 2010 May 21.
17 Structure-based design of potent and selective 2-(quinazolin-2-yl)phenol inhibitors of checkpoint kinase 2. J Med Chem. 2011 Jan 27;54(2):580-90. doi: 10.1021/jm101150b. Epub 2010 Dec 27.
18 Irinotecan induces senescence and apoptosis in colonic cells in vitro. Toxicol Lett. 2012 Oct 2;214(1):1-8. doi: 10.1016/j.toxlet.2012.08.004. Epub 2012 Aug 14.
19 Repairing of N-mustard derivative BO-1055 induced DNA damage requires NER, HR, and MGMT-dependent DNA repair mechanisms. Oncotarget. 2015 Sep 22;6(28):25770-83. doi: 10.18632/oncotarget.4514.
20 Long-term exposure to zidovudine delays cell cycle progression, induces apoptosis, and decreases telomerase activity in human hepatocytes. Toxicol Sci. 2009 Sep;111(1):120-30. doi: 10.1093/toxsci/kfp136. Epub 2009 Jun 18.
21 Triggering of transient receptor potential vanilloid type 1 (TRPV1) by capsaicin induces Fas/CD95-mediated apoptosis of urothelial cancer cells in an ATM-dependent manner. Carcinogenesis. 2009 Aug;30(8):1320-9. doi: 10.1093/carcin/bgp138. Epub 2009 Jun 5.
22 Oncogenic Potential of Bisphenol A and Common Environmental Contaminants in Human Mammary Epithelial Cells. Int J Mol Sci. 2020 May 25;21(10):3735. doi: 10.3390/ijms21103735.
23 Levonorgestrel enhances spermatogenesis suppression by testosterone with greater alteration in testicular gene expression in men. Biol Reprod. 2009 Mar;80(3):484-92.
24 Induction of APOBEC3C Facilitates the Genotoxic Stress-Mediated Cytotoxicity of Artesunate. Chem Res Toxicol. 2019 Dec 16;32(12):2526-2537. doi: 10.1021/acs.chemrestox.9b00358. Epub 2019 Nov 11.
25 The sunless tanning agent dihydroxyacetone induces stress response gene expression and signaling in cultured human keratinocytes and reconstructed epidermis. Redox Biol. 2020 Sep;36:101594. doi: 10.1016/j.redox.2020.101594. Epub 2020 May 29.
26 Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells. Toxicol Appl Pharmacol. 2012 Jan 1;258(1):51-60. doi: 10.1016/j.taap.2011.10.007. Epub 2011 Oct 18.
27 Checkpoint signaling, base excision repair, and PARP promote survival of colon cancer cells treated with 5-fluorodeoxyuridine but not 5-fluorouracil. PLoS One. 2011;6(12):e28862. doi: 10.1371/journal.pone.0028862. Epub 2011 Dec 15.
28 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
29 Mechanism study of goldenseal-associated DNA damage. Toxicol Lett. 2013 Jul 31;221(1):64-72. doi: 10.1016/j.toxlet.2013.05.641. Epub 2013 Jun 5.
30 Identifying the differential effects of silymarin constituents on cell growth and cell cycle regulatory molecules in human prostate cancer cells. Int J Cancer. 2008 Jul 1;123(1):41-50. doi: 10.1002/ijc.23485.
31 AMP-activated protein kinase signaling activation by resveratrol modulates amyloid-beta peptide metabolism. J Biol Chem. 2010 Mar 19;285(12):9100-13. doi: 10.1074/jbc.M109.060061. Epub 2010 Jan 14.
32 Testosterone augments polyphenol-induced DNA damage response in prostate cancer cell line, LNCaP. Cancer Sci. 2011 Feb;102(2):468-71. doi: 10.1111/j.1349-7006.2010.01791.x. Epub 2010 Dec 7.
33 ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res. 2014 Dec 1;74(23):6968-79.
34 Effect of ON 01910.Na, an anticancer mitotic inhibitor, on cell-cycle progression correlates with RanGAP1 hyperphosphorylation. Cancer Res. 2011 Jul 15;71(14):4968-76. doi: 10.1158/0008-5472.CAN-10-1603. Epub 2011 Jun 6.
35 1,2:5,6-dianhydrogalactitol inhibits human glioma cell growth in vivo and in vitro by arresting the cell cycle at G(2)/M phase. Acta Pharmacol Sin. 2017 Apr;38(4):561-570. doi: 10.1038/aps.2016.154. Epub 2017 Feb 20.
36 Regulation of genistein-induced differentiation in human acute myeloid leukaemia cells (HL60, NB4) Protein kinase modulation and reactive oxygen species generation. Biochem Pharmacol. 2009 Feb 1;77(3):384-96. doi: 10.1016/j.bcp.2008.10.035. Epub 2008 Nov 6.
37 Cellular impedance assays for predictive preclinical drug screening of kinase inhibitor cardiovascular toxicity. Toxicol Sci. 2013 Oct;135(2):402-13. doi: 10.1093/toxsci/kft167. Epub 2013 Jul 28.
38 Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
39 Superior efficacy of cotreatment with BET protein inhibitor and BCL2 or MCL1 inhibitor against AML blast progenitor cells. Blood Cancer J. 2019 Jan 15;9(2):4. doi: 10.1038/s41408-018-0165-5.
40 Methylisoindigo preferentially kills cancer stem cells by interfering cell metabolism via inhibition of LKB1 and activation of AMPK in PDACs. Mol Oncol. 2016 Jun;10(6):806-24. doi: 10.1016/j.molonc.2016.01.008. Epub 2016 Feb 4.
41 Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.
42 Caffeine inhibits the checkpoint kinase ATM. Curr Biol. 1999 Oct 7;9(19):1135-8. doi: 10.1016/s0960-9822(99)80486-2.
43 Molecular mechanism and inhibitory targets of dioscin in HepG2 cells. Food Chem Toxicol. 2018 Oct;120:143-154.
44 DNA damage responses in cells exposed to sulphur mustard. Toxicol Lett. 2012 Feb 25;209(1):1-10. doi: 10.1016/j.toxlet.2011.11.009. Epub 2011 Nov 18.
45 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
46 MCM-2 is a therapeutic target of Trichostatin A in colon cancer cells. Toxicol Lett. 2013 Jul 31;221(1):23-30. doi: 10.1016/j.toxlet.2013.05.643. Epub 2013 Jun 13.
47 Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
48 Inactivation of ATM/ATR DNA damage checkpoint promotes androgen induced chromosomal instability in prostate epithelial cells. PLoS One. 2012;7(12):e51108. doi: 10.1371/journal.pone.0051108. Epub 2012 Dec 18.
49 Toxicity mechanism of acrolein on DNA damage and apoptosis in BEAS-2B cells: Insights from cell biology and molecular docking analyses. Toxicology. 2022 Jan 30;466:153083. doi: 10.1016/j.tox.2021.153083. Epub 2021 Dec 24.
50 Fisetin-induced apoptosis of human oral cancer SCC-4 cells through reactive oxygen species production, endoplasmic reticulum stress, caspase-, and mitochondria-dependent signaling pathways. Environ Toxicol. 2017 Jun;32(6):1725-1741. doi: 10.1002/tox.22396. Epub 2017 Feb 9.
51 Molecular mechanism of anti-cancerous potential of Morin extracted from mulberry in Hela cells. Food Chem Toxicol. 2018 Feb;112:466-475. doi: 10.1016/j.fct.2017.07.002. Epub 2017 Jul 6.
52 p53 modulates the AMPK inhibitor compound C induced apoptosis in human skin cancer cells. Toxicol Appl Pharmacol. 2013 Feb 15;267(1):113-24. doi: 10.1016/j.taap.2012.12.016. Epub 2012 Dec 27.
53 Usnic acid induces apoptosis in human gastric cancer cells through ROS generation and DNA damage and causes up-regulation of DNA-PKcs and -H2A.X phosphorylation. Chem Biol Interact. 2020 Jan 5;315:108898. doi: 10.1016/j.cbi.2019.108898. Epub 2019 Nov 9.
54 Norcantharidin induces apoptosis of breast cancer cells: involvement of activities of mitogen activated protein kinases and signal transducers and activators of transcription. Toxicol In Vitro. 2011 Apr;25(3):699-707. doi: 10.1016/j.tiv.2011.01.011. Epub 2011 Jan 23.
55 Sterigmatocystin-induced checkpoint adaptation depends on Chk1 in immortalized human gastric epithelial cells in vitro. Arch Toxicol. 2017 Jan;91(1):259-270. doi: 10.1007/s00204-016-1682-2. Epub 2016 Feb 25.